Phase III VISION Study: ASCO 2021

Phase III VISION Study

Despite progress in the management of prostate cancer, there is a high unmet need for new targeted treatment choices to improve outcomes for patients affected with Metastatic Castration-Resistant Prostate Cancer (mCRPC). Improving current standard-of-care treatment to make the most of men’s mental and physical well-being was recognized as unmet research need to help alleviate the considerable patient burden of these common adverse outcomes. Men diagnosed with high-risk prostate cancer generally have surgery and/or radiotherapy as curative purposes.

To overcome this unmet need, key pharma companies are involved in mCRPC drug development include AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Janssen Pharmaceuticals, Hoffmann-La Roche, Pfizer, Astellas Pharma, Hinova Pharmaceuticals, Clovis Oncology, Innocrin Pharmaceutical, Trovagene, among others. However, one of the interesting research that is going on is the role of PSMA-target radioligand therapy, i.e. 177Lu-PSMA-617, which is under development by Novartis for the treatment of mCRPC.

Undoubtedly, Novartis has a strong radioligand therapy pipeline and remains in talks due to its significant buyouts. Earlier in 2017, Novartis completed the acquisition of Advanced Accelerator Applications (AAA) to gain the rights of Lutathera, a radioligand therapy for neuroendocrine tumors, strengthening its existing neuroendocrine franchise. For the same, it acquired 177Lu-PSMA-617 from Endocyte during a buyout in 2018 to expand the company’s capability in radiopharmaceuticals and build on assurance to transformational therapeutic platforms.

Why is 177Lu-PSMA-617 exclusive? 177Lu-PSMA-617 is a new Prostate-Specific Membrane Antigen (PSMA) targeted radioligand therapy for Metastatic Castration-Resistant Prostate Cancer. It is a type of precision cancer treatment that combines a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle). After administration into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells that express PSMA, a transmembrane protein, with high tumour-to-normal tissue uptake. This radioligand therapy is given as a systemic injection where it can directly target multiple sites of PSMA-positive prostate cancer in the body, including the bone and soft tissue, while evading the PSMA-negative cells. Lutetium-177 emits a very short-range β particle as well as γ emission – this advantage permits for a lower dose of radiation exposure to the bone marrow that may help it to be more bearable for myelotoxicity. The γ emission allows Lutetium-177 to be used as an imaging agent. What extremely important is an accurate diagnosis. The appearance of PSMA afore treatment with 177Lu-PSMA-617can only be determined using whole body PSMA-directed imaging, offering personalization of treatment so that the best course of therapy can be selected.

Consequently, in March 2021, Novartis announced the first interpretable results of the Phase III VISION study assessing the efficacy and safety of 177Lu-PSMA-617. The trial, as reported by the company, met both primary endpoints of overall survival and radiographic progression-free survival (rPFS) to accomplish the goal of becoming the targeted treatment for >80% of patients with advanced prostate cancer. Furthermore, the safety findings reported with the product proved to be consistent with what has been observed in prior clinical trials. The company is presenting this much-awaited data in the upcoming ASCO 2021(#LBA4 presentation). Owing to the successful results, Novartis is expected to file in 2021. The success of the phase III VISION study will help Novartis in generating a good return in the radioligand therapy market, which can further help in strengthening its pipeline activity in this program.

Following these positive results, in March 2021, Novartis also obtained exclusive worldwide rights to develop and commercialize therapeutic applications for a library of Fibroblast Activation Protein (FAP) targeting agents, including FAPI-46 and FAPI-74, through an assignment agreement with iTheranostics to expand its radioligand pipeline. Additionally, Novartis also had struck a deal with Artios Pharma to gain the acess to DNA damage response (DDR) targets with the potential to enhance its radioligand therapies.

The success of phase III trials offers Novartis a bright chance at generating a return on its outlay and provides a boost for its radiopharmaceutical strategy and the broader business. Analysts at DelveInsight believe that the use of 177Lu-PSMA-617 will be limited to patients with high expression of PSMA; however, as 60% to 80% of patients have high-grade prostate cancer, the PSMA limitation will still render Novartis with a significant chunk of the market to target. Additionally, considering that the phase III data is robust, we believe that Novartis can possibly expand its usage to earlier lines of treatment.